SCIN, also known as scinderin, is a calcium-dependent actin severing and capping protein. It is involved in regulating the F-actin cytoskeleton network, which is crucial for maintaining cell polarity, adhesion, proliferation, and migration. These functions are associated with various biological processes and disease-related pathways [5,7]. Genetic models, such as gene knockout mouse models, can be valuable for studying its functions.

In a conditional knockout (cKO) mouse model where the gene encoding the catalytic subunit Pik3c3 was specifically deleted in Sertoli cells, an accumulation of SCIN was observed. This led to the disorder and disassembly of the F-actin cytoskeleton, disrupting Sertoli cell polarity and impairing spermiogenesis. The results suggest that PIK3C3 negatively regulates SCIN, and the autophagy-lysosome pathway is involved in SCIN degradation [1]. In cancer-related studies, in gastric cancer, overexpressing miR-301a-5p promoted cell proliferation and motility by targeting SCIN, affecting the epithelial-mesenchymal transition (EMT) progression via STAT3 and NF-κB signaling [2]. In nasopharyngeal carcinoma, MEX3A promoted cancer progression via the miR-3163/SCIN axis by regulating NF-κB signaling. Depletion of SCIN reversed the oncogenic effects of MEX3A [3]. Lentivirus-mediated silencing of SCIN in human lung carcinoma cells inhibited cell proliferation, induced G0/G1 phase cell cycle arrest, and increased the expression of Cyclin B1, p21 and PARP [5]. Similar effects were seen in prostate cancer cells, where silencing of SCIN inhibited proliferation and induced G0/G1 cell cycle arrest through the regulation of cell cycle-related genes [7]. In triple-negative breast cancer, RSRC2 transcriptionally inhibited SCIN expression, and re-expression of SCIN reversed the cellular function changes caused by RSRC2 [6]. In acute myeloid leukemia, decreased SCIN expression associated with promoter methylation was a valuable biomarker for predicting adverse prognosis [4].

In conclusion, SCIN plays essential roles in maintaining the actin cytoskeleton and cell functions such as proliferation and cell cycle regulation. The use of KO/CKO mouse models and other loss-of-function experiments has revealed its significance in spermatogenesis and various cancer-related processes, providing insights into potential therapeutic targets for infertility and cancer treatment.

References:

1. Wang, Kehan, Kong, Feifei, Qiu, Yuexin, Hu, Zhibin, Li, Jing. 2023. Autophagy regulation and protein kinase activity of PIK3C3 controls sertoli cell polarity through its negative regulation on SCIN (scinderin). In Autophagy, 19, 2934-2957. doi:10.1080/15548627.2023.2235195. https://pubmed.ncbi.nlm.nih.gov/37450577/

2. Huang, Yingying, Du, Xiaoxiao, Chen, Xiangliu, Yang, Yan, Teng, Lisong. 2021. MiR-301a-5p/SCIN promotes gastric cancer progression via regulating STAT3 and NF-κB signaling. In Journal of Cancer, 12, 5394-5403. doi:10.7150/jca.59747. https://pubmed.ncbi.nlm.nih.gov/34405002/

3. Xiang, Xin-Xin, Liu, Yong-Liang, Kang, Yi-Fan, Lu, Xiang, Xu, Kai. 2022. MEX3A promotes nasopharyngeal carcinoma progression via the miR-3163/SCIN axis by regulating NF-κB signaling pathway. In Cell death & disease, 13, 420. doi:10.1038/s41419-022-04871-0. https://pubmed.ncbi.nlm.nih.gov/35490173/

4. Zhang, Zhi-Hui, Zhang, Wei, Zhou, Jing-Dong, Lin, Jiang, Qian, Jun. 2018. Decreased SCIN expression, associated with promoter methylation, is a valuable predictor for prognosis in acute myeloid leukemia. In Molecular carcinogenesis, 57, 735-744. doi:10.1002/mc.22794. https://pubmed.ncbi.nlm.nih.gov/29457658/

5. Liu, Hongxu, Shi, Daiwang, Liu, Tieqin, Yu, Zhanwu, Zhou, Chuanjiang. 2014. Lentivirus-mediated silencing of SCIN inhibits proliferation of human lung carcinoma cells. In Gene, 554, 32-9. doi:10.1016/j.gene.2014.10.013. https://pubmed.ncbi.nlm.nih.gov/25303873/

6. Zhao, Nan, Ni, Chunsheng, Fan, Shuai, Zhao, Xiulan, Liu, Tieju. 2023. RSRC2 Expression Inhibits Malignant Progression of Triple-Negative Breast Cancer by Transcriptionally Regulating SCIN Expression. In Cancers, 16, . doi:10.3390/cancers16010015. https://pubmed.ncbi.nlm.nih.gov/38201443/

7. Wang, Dong, Sun, Shu-Qing, Yu, Ying-Hao, Yang, Shun-Liang, Tan, Jian-Ming. 2013. Suppression of SCIN inhibits human prostate cancer cell proliferation and induces G0/G1 phase arrest. In International journal of oncology, 44, 161-6. doi:10.3892/ijo.2013.2170. https://pubmed.ncbi.nlm.nih.gov/24212916/